This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Peptide or protein aggregation is a field of great current interest, because of its close relationship to neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease. Although many researchers are working in the different aspects of the problems, however, due to their complexity, many questions remain to be answered. In this proposal, we will study one aspect of the self-aggregation problem of beta-amyloid peptides (Abeta), believed to be the main culprit of Alzheimer's disease. Among many levels of complications of the self-aggregation processes of Abeta, some characteristic features of amyloid formation emerge recently in both the experimental and simulational investigations. Particularly interesting is the suggested dock-lock mechanism for fibril growth, first suggested by experiments and then verified by simulations with short-peptide segments of Abeta. It is also suggested that such behavior might be general phenomena in fibril formation. Currently, computational studies on amyloid fibril formation process, aiming at elucidating directly and indirectly the detailed fibril formation pathways, are a hot subject. However, most of the simulations are restricted to short-segments of the Abeta peptides or based on coarse-grained models. In this report, we propose to study the fibril formation process of Abeta(1-42) under the all-atom explicit water condition. The time scale of the actual fibril formation process is from several hours to several days. To circumvent this time scale difficulty, we will start the simulation from an aggregated fibril already formed and then heat it up, until one monomer is about to leave the original fibril. At this point, we begin the simulation at room temperature (300 K) to observe the spontaneous deposition process of a monomer onto a preformed fibril. The objectives of this study are to verify the dock-lock mechanism of the fibril growth process, to find the main driving force of this fibril growth, to determine the size of the nuclei of the aggregation process, and to discover the roles of dehydration in the docking phase of the growth process. A long-range goal for the computer simulations of the fibril growth process of Abeta is to find ways to disrupt or slow down this neurodegerative process.